1. Field of the Invention
This invention relates to a sensor for measuring in real time a chemical species at ultra-low concentrations, even down to a single molecule.
2. Description of the Related Art
Chemical hazards, including hazards from biochemical substances, are a concern in an increasing number of arenas, including the modern battlefield (where the threat of chemical and biological warfare has returned), the workplace and the environment. Sensitive chemical sensors for detecting these hazards are needed. Chemical sensors with high sensitivity are also needed in other arenas, such as in the laboratory and on production lines, for conducting microtrace analysis, quality control, medical diagnostics, etc.
Such sensors should be highly selective, distinguishing between the species of interest and other species. The sensors should be reliable, not giving a significant number of false positives or false negatives. They should be adaptable to a wide variety of different species, and should be highly durable and transportable. They should operate in real-time. Most importantly, these sensors should be sensitive to extremely low concentrations, ideally being able to detect a single molecule of the target species.
One approach to ultra-low concentration detection is typified by Masai et al., Scanning tunneling microscopic immunoassay: A preliminary experiment., J. Vacuum Sci. Tech. A8 (1) 713-17 (1990). In this approach, an antibody is attached to a conductive substrate. This antibody is selected for immune complexation (antigen-antibody complexation) with the target antigen. The analyte solution, with the target antigen, is incubated with the treated substrate to form immune complexes on the substrate surface. The substrate is treated a second time with the antibody, to "sandwich" the target antigen between two antibodies. The immune complexes are then decorated with gold colloidal particles (gold with bioactive coatings), and these gold colloids are imaged by scanning tunneling microscopy (STM) or some other method.
This approach is very slow, entailing several incubation steps lasting several hours. This makes the process unsuitable for use in an alarm system.
This approach also entails scanning the substrate with the STM tip, looking for these gold colloidal particles. This reduces the reliability of the process. The reason for this difficulty is that these immune complexes have limited binding constants. The antigens of interest would spend most of their time in solution. Detecting a particular antigen would require the immune complex to be bound to a point on the substrate at the same time the tip was passing over the same point.
Another drawback to this method is that it is limited to high molecular weight species, because sandwiching the target species requires the target to be large enough to bind simultaneously to two sandwiching species.